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Characterization of HIF‐1α/Glycolysis Hyperactive Cell Population via Small‐Molecule‐Based Imaging of Mitochondrial Transporter Activity
The characterization of cancer stem‐like cells (CSCs) has profound implications for elucidating cancer biology and developing treatment strategies. Although surface markers are already used to identify CSCs, the expression of these markers is controversially linked to the phenotypes in different typ...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867035/ https://www.ncbi.nlm.nih.gov/pubmed/29593950 http://dx.doi.org/10.1002/advs.201700392 |
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author | Wang, Yang Liao, Xingyun Sun, Jianguo Yi, Bin Luo, Shenglin Liu, Tao Tan, Xu Liu, Dengqun Chen, Zelin Wang, Xin Shi, Chunmeng |
author_facet | Wang, Yang Liao, Xingyun Sun, Jianguo Yi, Bin Luo, Shenglin Liu, Tao Tan, Xu Liu, Dengqun Chen, Zelin Wang, Xin Shi, Chunmeng |
author_sort | Wang, Yang |
collection | PubMed |
description | The characterization of cancer stem‐like cells (CSCs) has profound implications for elucidating cancer biology and developing treatment strategies. Although surface markers are already used to identify CSCs, the expression of these markers is controversially linked to the phenotypes in different types of tumors and does not represent all functionally relevant of CSCs. Very recently, hyperactive HIF‐1α/glycolysis metabolic pathway is recognized as a master regulator of CSCs. In this study, a near‐infrared fluorescent small‐molecule, IR‐780, is identified for the exclusive characterization of human CSCs through the HIF‐1α/glycolysis dependent mitochondrial transporter ABCB10's activity. The results identified for the first time that ABCB10 is involved in the preferential uptake of IR‐780 in CSCs, which is regulated by HIF‐1α via the direct interaction with the binding site of ABCB10 gene promoter region. In addition, IR‐780 is demonstrated to conjugate with anticancer drug 5‐fluorouracil to act as a potential drug delivery carrier for CSC‐targeted therapy. Thus, the studies provide a new rational approach independent of surface markers to characterize CSCs via small‐molecule‐based imaging of HIF‐1α/glycolysis hyperactive metabolic pathway dependent mitochondrial transporter's activity, which holds promise for the further development of CSCs targeted diagnostic and therapeutic strategies. |
format | Online Article Text |
id | pubmed-5867035 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58670352018-03-28 Characterization of HIF‐1α/Glycolysis Hyperactive Cell Population via Small‐Molecule‐Based Imaging of Mitochondrial Transporter Activity Wang, Yang Liao, Xingyun Sun, Jianguo Yi, Bin Luo, Shenglin Liu, Tao Tan, Xu Liu, Dengqun Chen, Zelin Wang, Xin Shi, Chunmeng Adv Sci (Weinh) Full Papers The characterization of cancer stem‐like cells (CSCs) has profound implications for elucidating cancer biology and developing treatment strategies. Although surface markers are already used to identify CSCs, the expression of these markers is controversially linked to the phenotypes in different types of tumors and does not represent all functionally relevant of CSCs. Very recently, hyperactive HIF‐1α/glycolysis metabolic pathway is recognized as a master regulator of CSCs. In this study, a near‐infrared fluorescent small‐molecule, IR‐780, is identified for the exclusive characterization of human CSCs through the HIF‐1α/glycolysis dependent mitochondrial transporter ABCB10's activity. The results identified for the first time that ABCB10 is involved in the preferential uptake of IR‐780 in CSCs, which is regulated by HIF‐1α via the direct interaction with the binding site of ABCB10 gene promoter region. In addition, IR‐780 is demonstrated to conjugate with anticancer drug 5‐fluorouracil to act as a potential drug delivery carrier for CSC‐targeted therapy. Thus, the studies provide a new rational approach independent of surface markers to characterize CSCs via small‐molecule‐based imaging of HIF‐1α/glycolysis hyperactive metabolic pathway dependent mitochondrial transporter's activity, which holds promise for the further development of CSCs targeted diagnostic and therapeutic strategies. John Wiley and Sons Inc. 2018-01-09 /pmc/articles/PMC5867035/ /pubmed/29593950 http://dx.doi.org/10.1002/advs.201700392 Text en © 2018 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Full Papers Wang, Yang Liao, Xingyun Sun, Jianguo Yi, Bin Luo, Shenglin Liu, Tao Tan, Xu Liu, Dengqun Chen, Zelin Wang, Xin Shi, Chunmeng Characterization of HIF‐1α/Glycolysis Hyperactive Cell Population via Small‐Molecule‐Based Imaging of Mitochondrial Transporter Activity |
title | Characterization of HIF‐1α/Glycolysis Hyperactive Cell Population via Small‐Molecule‐Based Imaging of Mitochondrial Transporter Activity |
title_full | Characterization of HIF‐1α/Glycolysis Hyperactive Cell Population via Small‐Molecule‐Based Imaging of Mitochondrial Transporter Activity |
title_fullStr | Characterization of HIF‐1α/Glycolysis Hyperactive Cell Population via Small‐Molecule‐Based Imaging of Mitochondrial Transporter Activity |
title_full_unstemmed | Characterization of HIF‐1α/Glycolysis Hyperactive Cell Population via Small‐Molecule‐Based Imaging of Mitochondrial Transporter Activity |
title_short | Characterization of HIF‐1α/Glycolysis Hyperactive Cell Population via Small‐Molecule‐Based Imaging of Mitochondrial Transporter Activity |
title_sort | characterization of hif‐1α/glycolysis hyperactive cell population via small‐molecule‐based imaging of mitochondrial transporter activity |
topic | Full Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867035/ https://www.ncbi.nlm.nih.gov/pubmed/29593950 http://dx.doi.org/10.1002/advs.201700392 |
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